Longevity Paper Retracted

A study that identified several genes linked to extremely long life has been retracted due to technical errors in the sequencing chips used.

By Tia Ghose | July 21, 2011

Centenarian on her 100th birthdayFLICKR, JUHANSONIN

A paper about longevity genes has turned out to have a pretty short life itself. Science has retracted the July 2010 paper because inadequate controls and a technical glitch in a gene sequencing chip may have falsely suggested genetic links with extremely long life in humans.

The retracted study, which was cited 25 times, according to Google Scholar, claimed to have identified 19 genes strongly associated with longevity in more than 1,000 centenarians. Some, like the APOE gene, had been linked to longevity in other studies, but many were novel.

Within days of the paper’s publication, however, outside researchers pointed out that the otherwise meticulously designed study was flawed because the researchers had used a gene sequencing chip, the Illumina 610-Quad, which can produce some false positive associations. That in itself would not have been a problem, except that the group only used those chips for the centenarians. For the control group, they used several different types of chip known to produce fewer false positives.

A few weeks later, Science issued a notice that the authors, Boston University biostatistician Paola Sebastiani and colleagues, were reanalyzing their data because of a technical problem with the chips used to identify the genetic links. After an exhaustive review, the authors resubmitted the results in December 2010—with some differing details, but the main conclusions intact.

But it wasn’t enough. Ultimately, the authors voluntarily retracted the article after Science decided the revised paper did not meet their publication standards--standards that some in the scientific community are questioning.

“There is nothing wrong with what this data is saying at the end of the day,” said Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine of Yeshiva University, who was not involved in the study. “I really feel that this retraction was not totally appropriate.”

For instance, one requirement that Science says the authors didn’t meet was the replication of the original paper findings in a separate sample of 100-year-olds. But the journal didn’t require the original paper to include a replication sample, Barzilai said, so it’s unclear why it’s needed now. In addition, finding a new sample of centenarians to confirm their original results is unrealistic, given that only about 1 in 6,000 of us makes it to 100, Barzilai said.

Despite the retraction, the underlying hypothesis that certain genes are associated with longer life is still solid, said David Goldstein, a molecular biologist at Duke University, who was one of the first researchers to raise the potential problem. “I don't think this will have any adverse effects on longevity genetics,” he said. “People will keep working on it. The authors too, I hope!”

The researchers “are pursuing alternative publication of the corrected results” in another journal, Sebastiani said in a prepared statement. She declined The Scientist’s request for further comment until the new paper is published.

Science also declined to comment further on the paper, though the retraction statement emphasized “that there was no misconduct by Sebastiani and colleagues.”

They can also look at all of their positives and determine if other genes in the same pathway are also positive. I have used this method and I recommend it as a way of removing noise. The probability of just one single transcript in a pathway being upregulated (or downregulated) being real is extremely low. By taking a look at the exact sequence that is supposed to be on the chip on that location and using a tool like Mfold (mfold.rna.albany.edu/?q=mfold) to examine probability of alternative bindings to it, they can also shore up their data. It's possible the data can't be rescued, but then again, it may be possible.

They can also look at all of their positives and determine if other genes in the same pathway are also positive. I have used this method and I recommend it as a way of removing noise. The probability of just one single transcript in a pathway being upregulated (or downregulated) being real is extremely low. By taking a look at the exact sequence that is supposed to be on the chip on that location and using a tool like Mfold (mfold.rna.albany.edu/?q=mfold) to examine probability of alternative bindings to it, they can also shore up their data. It's possible the data can't be rescued, but then again, it may be possible.

They can also look at all of their positives and determine if other genes in the same pathway are also positive. I have used this method and I recommend it as a way of removing noise. The probability of just one single transcript in a pathway being upregulated (or downregulated) being real is extremely low. By taking a look at the exact sequence that is supposed to be on the chip on that location and using a tool like Mfold (mfold.rna.albany.edu/?q=mfold) to examine probability of alternative bindings to it, they can also shore up their data. It's possible the data can't be rescued, but then again, it may be possible.